Transcription elongation factors stimulate the activity of RNA polymerases (RNAPs) by increasing the overall elongation rate and the completion of RNA chains. One group of such factors, which includes E. coli GreA, GreB, and eukaryotic SII (TFIIS), acts by inducing hydrolytic cleavage of the transcript within the RNAP, followed by release of the 3'-terminal fragment. We have solved the structure of E.coli GreA to a resolution of 2.2 A. The structure contains a very unusual N-terminal domain consisting of an antiparallel a-helical coiled-coil dimer which extends into solution. Crosslinking studies show that a site near the tip of the coiled-coil 'finger' plays a direct role in the transcript cleavage reaction by contacting the 3'-end of the transcript. The structure exhibits and unusual asymmetric charge distribution. One face of the protein is highly acidic, whereas the opposite face is neutral except for a small basic patch. These properties suggest a model of how GreA interacts with the elongating RNAP complex. It is not possible at this point to propose a more detailed model of how GreA induces transcript cleavage, but the structure now allows testing of specific elements by biochemical and genetic means. Guided by the X-ray crystal structure of GreA, we are using site-directed mutagenesis to dissect the structure/function relationship of GreA. Once the mutant proteins are prepared, we depend on mass spectrometry to determine that we have the correct mutant, and that it is free of native GreA. We hope that elucidating the mechanisms of the transcript cleavage reaction induced by GreA will shed light on the mechanism of RNA activity and elongation itself.